Abstract 4181: Chronic stress and beta adrenergic signaling promote angiogenesis and prostate cancer progression through suppressing the expression of Thrombospondin 1

Abstract

Abstract Several recent studies have revealed that the activation of beta adrenergic signaling induced by chronic biobehavioral stress promotes the progression of ovarian, breast and prostate cancers. Conversely, the use of hypertension medicine, beta blockers (beta adrenergic antagonists), has been found to be associated with better prognosis in several human cancers. Although the beta adrenergic signaling has been shown to be activated by chronic stress and responsible for promoting cancers, the mechanisms through which beta adrenergic signaling promotes tumor angiogenesis and cancer progression are still unclear. We found that chronic stress and activation of beta adrenergic signaling suppressed the expression of Thrombospondin 1 (TSP1) in prostate cancer cells in vitro, as well as in mouse xenograft tumors in vivo, which in turn promoted tumor angiogenesis and cancer progression. TSP1 was the first endogenous angiogenesis inhibitor to be discovered and its down-regulation is associated with increased angiogenesis. We recently demonstrated that G-protein coupled receptor kinase 3 (GRK3, ADRBK2) promotes angiogenesis and prostate cancer progression through suppressing TSP1. Interestingly, GRK3 expression is up-regulated by chronic stress and activation of beta adrenergic signaling, suggesting that GRK3 acts as a mediator for chronic stress and beta adrenergic signaling in repressing TSP1 expression. Taken together, these results suggest that beta adrenergic signaling pathway stimulates angiogenesis through GRK3 mediated suppression of TSP1. Citation Format: Mohit M. Hulsurkar, Meixiang Sang, Haiping Song, Wenliang Li. Chronic stress and beta adrenergic signaling promote angiogenesis and prostate cancer progression through suppressing the expression of Thrombospondin 1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4181. doi:10.1158/1538-7445.AM2015-4181